In conclusion, these studies elucidate a novel mechanism by which sustained adrenergic stimulation contributes to cardiac hypertrophy and HF by increasing PDE4D via cAMP-PKA signaling, which in turn reduces cAMP-PKA activity, resulting in cardiomyocyte hypertrophy and mitochondrial injury via inhibition of CREB-SIRT1 signaling-mediated mitophagy. This evidence concerns the gene SIRT1 and cardiac hypertrophy.